This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Internal ribosome entry sites (IRESs) are functional RNA elements that can directly recruit ribosomes to an internal position of the mRNA in a cap-independent manner to initiate translation. Recently, IRES elements have attracted much attention for their critical roles in various processes including translation initiation of a new type of RNA, circular RNA (circRNA), with no 5′ cap to support classical cap-dependent translation. Thus, an integrative data resource of IRES elements with experimental evidence will be useful for further studies. In this study, we present IRESbase, a comprehensive database of IRESs, by curating the experimentally validated functional minimal IRES elements from literature and annotating their host linear and circular RNAs. The current version of IRESbase contains 1328 IRESs, including 774 eukaryotic IRESs and 554 viral IRESs from 11 eukaryotic organisms and 198 viruses, respectively. As IRESbase collects only IRES of minimal length with functional evidence, the median length of IRESs in IRESbase is 174 nucleo-tides. By mapping IRESs to human circRNAs and long non-coding RNAs (lncRNAs), 2191 cir-cRNAs and 168 lncRNAs were found to contain at least one entire or partial IRES sequence. IRESbase is available at http://reprod.njmu.edu.cn/cgi-bin/iresbase/index.php.

Circular RNAs (circRNAs), covalently closed continuous RNA loops, are generated from cognate linear RNAs through back splicing events, and alternative splicing events may gener-ate different circRNA isoforms at the same locus. However, the challenges of reconstruction and quantification of alternatively spliced full-length circRNAs remain unresolved. On the basis of the internal structural characteristics of circRNAs, we developed CircAST, a tool to assemble alter-natively spliced circRNA transcripts and estimate their expression by using multiple splice graphs.Simulation studies showed that CircAST correctly assembled the full sequences of circRNAs with a sensitivity of 85.63％-94.32％and a precision of 81.96％-87.55％. By assigning reads to specific iso-forms, CircAST quantified the expression of circRNA isoforms with correlation coefficients of 0.85-0.99 between theoretical and estimated values. We evaluated CircAST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circRNAs and identified 380 cir-cRNAs with full-length sequences different from those of their corresponding cognate linear RNAs. RT-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms, thus further indicating the good performance of CircAST, especially for isoforms with low abundance. We also applied CircAST to published experimental data and observed substantial diversity in circular transcripts across samples, thus suggesting that circRNA expression is highly regulated. CircAST can be accessed freely at https://github.com/xiaofengsong/CircAST.

AIM: To explore the influence of Huqi San on the Hedgehog signaling pathway in rats with prehe-patocarcinoma.METHODS: The model of prehepatocarcinoma in the rats was established by a modified solt-farber method.The rats were intragastric administrated with Huqi San solution for 3 d after subtotal hepatectomy.Four weeks after administration of the Huqi San solution, the hepatic damage was observed by histopathological analysis.The protein expression of glutathione S-transferase-π (GST-π), alpha-fetoprotein (AFP), OV6, albumin (ALB) and glioma-associated oncogene homolog 2 (Gli2) was detected by immunohistochemistry and immunofluorescence staining.The expression of Sonic hedgehog (Shh), Smoothened (Smo), Gli2, cyclin D and cyclin E at mRNA and protein levels in the rats was determined by RT-qPCR and Western blot, respectively.The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were assayed using diagnostic kits.RESULTS: Compared with model group, Huqi San decreased the serum levels of ALT, AST and GGT, and alleviated the pathological changes in prehepatocarcinoma rats.Huqi San inhibited the protein expression of GST-π and AFP (P<0.05) in the prehepatocarcinoma rats.Huqi San also promoted the protein expression of OV6 and ALB (P<0.05).Furthermore, Huqi San activated Hedgehog signaling pathway and its downstream targeting molecules such as Shh, Smo, Gli2, cyclin D and cyclin E.In addition, the results in vitro showed that Huqi San may activate Hedgehog signaling pathway and promoted oval cell proliferation.CONCLUSION: Huqi San not only promotes hepatic progenitor cell proliferation, but also induces hepatic progenitor cell differentiation and inhibits prehepatocarcinoma in the rats probably via activating Hedgehog signaling pathway.

Objective To explore the possible mechanism of action of telomerase in hepatic precancerous lesions, and the regulatory effect of a Chinese medicine prescription HU Qi Shan ( HQS) and its principal drug mistletoe alkali on the telomerase activity in rat liver tissues.Methods Rat model of hepatic precancerous lesions was established by Solt-Farber two-step protocol.The model rats were randomly divided into 5 groups, including the model group, high-dose HQS [8 g/(kg· d)] group, low-dose HQS [4 g/(kg· d)] group, and mistletoe alkali[8 mg/(kg· d)] group.γ-Glutamy-transpeptidase (γ-GT) was analyzed by immunohistochemistry.AFP was detected by immunofluorescence technique.The telomerase activity was detected using a quantitative telomerase detection kit.The expression of NF-κB P65 was detected by immunohistochemistry.The cytoplasmic protein IκB-αwas detected by western blotting.Results After treated with HQS and mistletoe alkali, the areas ofγ-GT-positive foci and number of AFP-positive cells in the liver tissus were significantly decreased than those of the model group ( P<0.05 for both) , the telomerase activity was decreased, the number of NF-κB P65-positive cells was also decreased ( P <0.05 ) , whereas the intracytoplasmic expression of IκB-αproteins was significantly increased ( P <0.05 ) .Conclusions HQS and mistletoe alkali can suppress the telomerase activity.Its possible mechanism may be through inhibition of the over-expressed apoptosis-related genes such as NF-κB P65 and increase the expression of IκB-αdecreasing the telomerase activity.

Objective:To improve the CT bulb tube cooling rate and the testing method of the CT bulb tube temperature, and provide more stable platform for better bulb tube protection and longer life-span. Methods: The designed specified cold air machine could transfer the dry cold wind into machine rack, which can lower the ambient temperature of the machine rack and increase the air flow inside the machine rack and promote the efficiency of the heat exchange of the bulb tube oil cooling circuit. Results:the design of this system’s joint is light and handy, which could collect the instantaneous temperature change of the bulb tube, and carry out simple man-machine interaction monitoring. Conclusion:According to the bulb tube oil-way temperature and ambient temperature and relative humidity, the computer can dynamically adjust the refrigerating capacity and operation/cease of the air cooler. Then it can constitute the closed control loop, and accelerate the efficiency of the bulb tube’s heat dissipation, and promote the heat capacity of the bulb tube equivalently.

Objective To study the changes and significance of plasma atrial natriuretic peptide (ANP),endothehn-1 (ET-1),von Willebrand factor (vWF) levels in newborns with persistent pulmonary hypertension (PPHN) after the treatment of sildenafil.Methods Sixty-six cases with PPHN group and 40 cases with non-PPHN (control group) were enrolled.PPHN group was in the treatment of sildenafil.Collected the blood when before the treatment of sildenafil and 3,7 d after treatment,respectively.Arterial blood gas were done and pulmonary arterial systolic pressure (PASP) was measured before treatment and 3,7 d after treatment,and by the same time recording pulse oxygen saturation (SpO2).Plasma ANP,ET-1,vWF levels were measured by ELISA method.Results The levels of PASP,SpO2 arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2) and plasma ANP,ET-1,vWF in PPHN group before treatment [(66.5 ± 13.4)mm Hg (1 mm Hg =0.133 kPa),0.726 ±0.531,(46.3 ±7.2)mm Hg,(59.2 ± 7.4) mm Hg,(272.6 ± 20.3)ng/L,(221.3 ± 24.3) ng/L,(142.5 ± 20.3)％] compared with controlgroup [(25.0±6.2) mm Hg,0.896 ± 0.767,(88.3 ±7.6) mm Hg,(41.1 ±6.1) mm Hg,(68.4 ± 7.9) ng/L,(39.8 ± 6.5) ng/L,(95.3 ± 18.5)％] were statistically significant(P ＜ 0.05).Their levels in PPHN group 3 dafter treatment[(48.3 ± 3.2) mm Hg,0.841 ± 0.416,(73.6 ± 9.3)mm Hg,(50.5 ± 7.2) mm Hg,(102.6 ±20.3) ng/L,(79.6 ± 15.2) ng/L,(103.6 ± 14.1)％] were significantly improved,there was significantdifference compared with before treatment and control group(P ＜ 0.05).Their levels in PPHN group 7 d aftertreatment [(25.2 ± 3.6) mm Hg,0.882 ± 0.724,(85.4 ± 7.4) mm Hg,(40.2 ± 6.4) mm Hg,(64.4 ± 3.6)ng/L,(37.3 ± 5.4)ng/L,(92.9 ± 11.7)％] were significantly improved,there was significant difference compared with 3 d after treatment (P ＜ 0.05),the difference was no statistically significant compared with control group (P＞ 0.05).Linear correlation analysis showed that ANP,ET-1,vWF and PASP,PaCO2 were significantly positively correlated (P ＜ 0.01),ANP,ET-1,vWF and SpO2,PaO2 were significantly negatively correlated (P＜ 0.01).On the basis of cardiac ultrasound monitoring PASP,ANP evaluation of the efficacy of sildenafil sensitivity was 82.2％,specificity was 83.4％ ;ET-1 was 86.4％ and 87.6％; vWF was 85.1％ and 84.7％.Conclusion ANP,ET-1,vWF may play an important role in the mechanism of the treatment of PPHN by sildenafil,and could be used as an objective index to evaluate the effect of sildenafil on PPHN.